Efficacy of Integrated Risk Score Using Omics-Based Biomarkers for the Prediction of Acute Rejection in Kidney Transplantation: A Randomized Prospective Pilot Study.

Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs.

Global lineage evolution pattern of sars-cov-2 in Africa, America, Europe, and Asia: A comparative analysis of variant clusters and their relevance across continents.

Objective: The objective of this study is to provide a comparative analysis of variant clusters and their relevance across Africa, America, Europe, and Asia, in order to understand the evolutionary patterns of the virus across different regions and to inform the development of targeted interventions and genomic surveillance eforts. Methods: The study analyzed the global lineage evolution pattern of 74, 075 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from 32 countries across four continents, focusing on variant clusters and their relevance across regions. Variants were weighted according to their hierarchical level. The correlation between variants was visualized through Dimensionality reduction analysis and Pairwise Pearson's correlation. We presented a reconstructed phylogenetic tree based on correlation analysis and variant weights. Results: The analysis revealed that each continent had distinct variant clusters and different evolutionary patterns. The Americas had two clustered variants before lineage divergence and a downstream confluence lineage, Europe had bifurcation into two global lineages with an early occurrence of certain cluster while Asia had a downstream confluence of two large lineages diverging by two distinct clusters. Based on the cluster patterns of shared variants of the SARS-CoV-2 virus, Africa demonstrated a relatively clear distinction among three distinct regions. Conclusions: The study provides insights into the evolutionary patterns of SARS-CoV-2 and highlights the importance of international collaboration in tracking and responding to emerging variants. The study found that the global pandemic was driven by Omicron variants that evolved with significant differences between countries and regions, and with different patterns across continents.

A Case of Multiple Necrotic Dyskeratotic Cells within the Upper Epidermis and Horny Layer Revealing Persistent Papules and Plaques of Adult-Onset Still's Disease.

It is important to differentiate violaceous to dusky red papules and plaques that widely persist on the trunk and extremities because there are dermatoses that could be fatal, such as lupus erythematosus, dermatomyositis, drug eruptions, and graft-versus-host disease. Dyskeratotic cells only in the upper epidermis and horny layer are not well known, but it is a distinctive histopathological pattern of atypical type of rash of adult-onset Still's disease (AOSD). AOSD rash is a transient salmon-colored rash that occurs and disappears with fever; however, an atypical type of rash called "persistent dermal plaque" or "persistent pruritic eruptions" has also been reported. It occurs and persists even after fever subsides. Herein, we describe a case with necrotic dyskeratotic cells in the upper epidermis and horny layer without AOSD symptoms lasting for five years.

Protaetia Brevitarsis-Derived Protein Hydrolysate Reduces Obesity-Related Colitis Induced by High-Fat Diet in Mice through Anti-Inflammatory Pathways.

Ulcerative colitis is an inflammatory bowel disease characterized by inflammation in the mucosal and submucosal layers of the colon. Obesity is closely related to the occurrence and progression of colitis. The most plausible mechanism linking obesity and colitis is an excessive adipogenesis-related inflammatory response, which causes mucosal dysfunction. Obesity and colitis are linked by several etiologic mechanisms, including excessive adipogenesis, lipotoxicity, pro-inflammatory adipokines/cytokines, macrophage polarization, oxidative stress, endoplasmic reticulum (ER) stress, and gut microbiota. These low-grade enteric inflammations cause mucosal layer damage, especially goblet cell dysfunction through mucin 2 (MUC2) misfolding, ultimately leading to colitis. Inhibiting the inflammatory response can be the most effective approach for treating obesity-related colitis. We focused on the anti-inflammatory effects of polyphenols in Protaectia brevitas larvae. The P. brevitas was prepared as a low molecular protein hydrolysate (PHPB) to increase the concentration of anti-inflammatory molecules. In the current study, we investigated the anti-inflammatory effect of PHPB in an obesity-induced colitis mouse model. Compared with the high-fat diet (HFD) group, the group treated with PHPB exhibited reduced body/organ/fat weight, appetite/food intake inhibition, hypolipidemic effect on ectopic fat, and anti-adipogenic mechanism through the AMPK signaling pathway. Furthermore, we observed attenuated expression of PPARγ and C/EBPα, inhibition of pro-inflammatory molecules, stimulation of anti-inflammatory molecules, probiotic-like effect against obesogenic gut microbiota, inhibition of macrophage polarization into M1, suppression of oxidative/ER stress, and reduction of Muc2 protein misfolding in colon. These diverse anti-inflammatory responses caused histological and functional recovery of goblet cells, eventually improving colitis. Therefore, our findings suggest that the protein hydrolysate of Protaetia brevitarsis can improve obesity-related colitis through its anti-inflammatory activities.

Recurrent C3 Glomerulonephritis along with BK-Virus-Associated Nephropathy after Kidney Transplantation: A Case Report.

C3 glomerulonephritis (C3GN) is a rare cause of end-stage kidney disease and frequently recurrent in allografts following kidney transplantation (KT). Herein, we describe the case of a kidney transplant recipient who developed recurrent C3GN along with BK-virus-associated nephropathy (BKVAN) following KT. A 33-year-old man diagnosed with membranoproliferative glomerulonephritis 17 years ago underwent preemptive KT with a donor kidney from his aunt. Proteinuria gradually increased after 3 months following KT, and graft biopsy was performed 30 months after KT. Histopathological examination revealed recurrent C3GN. The dosages of triple immunosuppressive maintenance therapy agents were increased. Subsequently, serum C3 levels recovered to normal levels. However, at 33 months following KT, the BK viral load increased and graft function gradually deteriorated; a second graft biopsy was performed at 46 months following KT, which revealed BKVAN and decreased C3GN activity. The dosages of immunosuppressive agents were decreased; subsequently, BKVAN improved and graft function was maintained with normal serum C3 levels at 49 months following KT. This case indicates that C3GN is highly prone to recurrence following KT and that immunosuppressive therapy for C3GN increases the risk of BKVAN.

Five- and 10-year survival in extramammary Paget's disease: A focus on wide local excision.

AIM: This study aimed to analyze extramammary Paget's disease (EMPD)-specific survival, overall survival, and recurrence rate (RR) in patients with EMPD in South Korea, with a focus on wide local excision. METHODS: We retrospectively reviewed the medical records of patients with EMPD from 1993 to 2020 at Kyungpook National University Hospital. We determined the survival and RRs after wide local excision. RESULTS: A total of 95 patients (66 males and 29 females; mean age 67.4 years) were included. The 5-year disease-specific survival and overall survival were 91.8% and 79.3%, respectively, whereas the 10-year rates were 81.6% and 64.7%, respectively. No significant sex differences were observed. Seventy-five patients (78.9%) underwent wide local excision. Mucosal involvement and lymphadenopathy were identified as the significant prognostic factors of disease-specific survival in multivariate analysis. The RR was 14.7% in patients who underwent wide local excision: seven local, two regional, and two distant metastases, with a mean recurrence-free interval of 42.3 months. CONCLUSION: Based on the survival and RRs obtained, surgical treatment of EMPD with wide local excision provides fair curative resection. PRACTITIONER POINTS: Wide local excision can be a feasible treatment option for extramammary Paget's disease.

Renal Sarcoidosis-like Reaction Induced by PD-1 Inhibitor Treatment in Non-Small Cell Lung Cancer: A Case Report and Literature Review.

Monoclonal antibodies directed against immune checkpoint proteins have been widely used to treat various cancers and have resulted in favorable clinical outcomes. Despite these beneficial properties, immune checkpoint inhibitors (ICIs) can induce side effects called immune-related adverse events, including sarcoidosis-like reactions (SLR) across multiple organs. Here, we report a case of renal SLR after ICI treatment, and we review the related literature. A 66-year-old Korean patient with non-small cell lung cancer was referred to the nephrology clinic for renal failure after the 14th pembrolizumab treatment dose. A renal biopsy revealed multiple epithelioid cell granulomas, with several lymphoid aggregates in the renal interstitium and a moderate degree of inflammatory cell infiltration in the tubulointerstitium. A moderate dose of steroid therapy was initiated, and the serum creatinine level partially recovered after four weeks of treatment. Judicious monitoring of renal SLR is, therefore, required during ICI therapy, and a timely diagnosis by renal biopsy and appropriate treatment are important.

Consensus Definition of Blood Samples from the Subcategorized Normal Controls in the Korea Biobank Network.

A control group is defined as a group of people used for comparison. Depending on the type of study, it can be a group of healthy people or a group not exposed to risk factors. It is important to allow researchers to select the appropriate control participants. The Korea Biobank Project-sponsored biobanks are affiliated with the Korea Biobank Network (KBN), for which the National Biobank of Korea plays a central coordinating role among KBN biobanks. KBN organized several working groups to address new challenges and needs in biobanking. The "Normal Healthy Control Working Group" developed standardized criteria for three defined control groups, namely, normal, normal-plus, and disease-specific controls. Based on the consensus on the definition of a normal control, we applied the criteria for normal control participants to retrospective data. The main reason for exclusion from the "Normal-plus" group was blood test results beyond 5% of the reference range, including hypercholesterolemia. Subclassification of samples of normal controls by detailed criteria will help researchers select optimal normal controls for their studies.

De Novo Crescentic Glomerulonephritis Following COVID-19 Infection: A Pediatric Case Report.

As the global coronavirus disease 2019 (COVID-19) pandemic continues to sweep across the globe, reports of kidney involvement in adult patients infected with COVID-19 have been documented, and recently, cases in the pediatric population have also been reported. This report highlights the case of an 11-year-old boy who developed acute kidney injury presenting as gross hematuria, proteinuria, and hypertension immediately after a COVID-19 infection. A renal biopsy allowed us to diagnose the patient with post-COVID-19 infection-associated de novo crescentic immune-mediated glomerulonephritis. Oral prednisolone and cyclophosphamide treatments were initiated after methylprednisolone pulse therapy administration. Currently, the patient is receiving medical treatment for five weeks, and his renal function is gradually recovering. Previous studies have suggested that, although quite rare, a variety of kidney complications can occur after COVID-19 infection or vaccination, and it is recommended to monitor renal function through evaluation. Herein, we report a pediatric case of post-COVID-19 infection-associated de novo crescentic immune-mediated glomerulonephritis consistent with rapidly progressive glomerulonephritis.

CD69 flow cytometry to complement interferon-γ release assay for active tuberculosis.

BACKGROUND: The interferon-γ (IFN-γ) release assay (IGRA) is widely used to diagnose tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb). However, indeterminate IGRA results due to "high Nil" or "low PHA" responses limit its clinical utility. We developed a novel assay using CD69 flow cytometry (FC) to complement IGRA. METHODS: CD69 FC measures the surface CD69 expression on T cells prior to centrifugation to harvest the plasma for IGRA. T cell responses against Mtb antigen 1 (Ag1) or Ag2 were measured using three-color FC (CD3, CD4, and CD69) in TB (n = 140) and non-TB groups (n = 117). The cutoff values of Δ%CD69bright cells (stimulated minus unstimulated) for CD4+ and CD4- T cells were established based on healthy individuals (n = 63). The assay performances of CD69 FC and IGRA were compared. RESULTS: In subjects with determinate IGRA results ("positive" or "negative"; n = 216), the diagnostic accuracies of CD69 FC (90.3%) and IGRA (87.0%) were not significantly different (p = 0.31). For indeterminate IGRA results (n = 40), CD69 FC attained a diagnostic accuracy of 92.5%. The CD4+ /CD4- ratio within CD69bright T cells measured by CD69 FC was significantly higher (p < 0.05) in the active TB group (6.39 ± 132.05; n = 72) than in other CD69 FC-positive subjects (2.84 ± 15.36; n = 63) (p < 0.05), whereas CD8 responses expected by IGRA (difference of IFN-γ levels between Mtb Ag tubes) did not differ significantly (0.00 ± 9.18 and 0.00 ± 4.25, respectively, IU/ml; p = 0.58). CONCLUSIONS: We demonstrated the potential of CD69 FC as a simple, rapid assay for clarifying indeterminate IGRA results and identifying active TB. With further improvements, CD69 FC may complement the IGRA to enhance TB risk stratification in the routine diagnostic workup.

Comparison of diagnostic performances of slow-pull suction and standard suction in endoscopic ultrasound-guided fine needle biopsy for gastrointestinal subepithelial tumors.

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is integral to the diagnosis of gastrointestinal (GI) subepithelial tumors (SETs). The impact of different EUS-FNB tissue sampling techniques on specimen adequacy and diagnostic accuracy in SETs has not been fully evaluated. This study aimed to compare the diagnostic outcomes of slow-pull (SP) and standard suction (SS) in patients with GI SETs. METHODS: In this retrospective comparative study, 54 patients were enrolled. Medical records were reviewed for location and size of the target lesion, FNB needle type/size, technical order, specimen adequacy, diagnostic yield, and adverse events. The acquisition rate of adequate specimens and diagnostic accuracy were compared according to EUS-FNB techniques. RESULTS: The mean lesion size was 42.6±36.4 mm, and most patients were diagnosed with GI stromal tumor (75.9%). The overall diagnostic accuracies of the SP and SS techniques were 83.3% and 81.5%, respectively (p=0.800). The rates of obtaining adequate core tissue were 79.6% and 75.9%, respectively (p=0.799). No significant clinical factors affected the rate of obtaining adequate core tissue, including lesion location and size, FNB needle size, and final diagnosis. CONCLUSION: SP and SS had comparable diagnostic accuracies and adequate core tissue acquisition for GI SETs via EUS-FNB.

Relationship between gallstones and interstitial cells of Cajal in the gallbladder.

INTRODUCTION: A high percentage of patients with gallstones exhibit abnormalities in gallbladder emptying, and gallstones are often associated with gallbladder contraction. Interstitial cells of Cajal (ICC) in the gallbladder are involved in the generation and spreading of spontaneous contractions of the gallbladder. This study examined the relationship among the number of gallbladder ICC, gallbladder contractility, and gallstones. MATERIALS AND METHODS: Forty-six patients, who underwent cholecystectomy within 3 months of enduring a gallbladder ejection fraction scan, were enrolled in this study. ICC were identified using a microscope after immunohistochemical staining for CD117/c-kit. Five high-power field (magnification 400×) units were randomly assigned, and the number of ICC in the mucosal and muscular layers was counted. These counts were compared according to the sex, age, reason for cholecystectomy, presence of gallstone, presence of gallbladder polyp, gallbladder ejection fraction, and gallbladder size for each patient. RESULTS: The number of ICC in the mucosal layer was increased in the male participants (154.4 ± 73.9) compared with the female participants (107.3 ± 75.2); however, the ICC in the muscular layer was not different between the 2 groups. Additionally, the ICC in the mucosal and muscular layers did not differ according to age, cause of cholecystectomy, number of stones, stone character, stone diameter, or the presence of polyps. A larger gallbladder size was correlated with a decreased number of ICC in the muscular layer of the gallbladder. Additionally, when the number of gallbladder stones was increased, the number of ICC in the muscular layer of the gallbladder was decreased; however, there was no significant correlation between the number of ICC in the mucosal layer of the gallbladder and any of the following factors: age, GBEF, gallbladder size, stone number, or diameter. Furthermore, there was no significant correlation between the number of ICC in the muscular layer of the gallbladder, regardless of age, GBEF, and stone diameter. CONCLUSION: Although we were unable to achieve significant results regarding the relationship between GBEF and ICC, this is the first human study to reveal the relationship among ICC, gallbladder size, and the number of gallstones.

Asymmetric Contribution of Blastomere Lineages of First Division of the Zygote to Entire Human Body Using Post-Zygotic Variants.

BACKGROUND: In humans, after fertilization, the zygote divides into two 2n diploid daughter blastomeres. During this division, DNA is replicated, and the remaining mutually exclusive genetic mutations in the genome of each cell are called post-zygotic variants. Using these somatic mutations, developmental lineages can be reconstructed. How these two blastomeres are contributing to the entire body is not yet identified. This study aims to evaluate the cellular contribution of two blastomeres of 2-cell embryos to the entire body in humans using post-zygotic variants based on whole genome sequencing. METHODS: Tissues from different anatomical areas were obtained from five donated cadavers for use in single-cell clonal expansion and bulk target sequencing. After conducting whole genome sequencing, computational analysis was applied to find the early embryonic mutations of each clone. We developed our in-house bioinformatics pipeline, and filtered variants using strict criteria, composed of mapping quality, base quality scores, depth, soft-clipped reads, and manual inspection, resulting in the construction of embryological phylogenetic cellular trees. RESULTS: Using our in-house pipeline for variant filtering, we could extract accurate true positive variants, and construct the embryological phylogenetic trees for each cadaver. We found that two daughter blastomeres, L1 and L2 (lineage 1 and 2, respectively), derived from the zygote, distribute unequally to the whole body at the clonal level. From bulk target sequencing data, we validated asymmetric contribution by means of the variant allele frequency of L1 and L2. The asymmetric contribution of L1 and L2 varied from person to person. CONCLUSION: We confirmed that there is asymmetric contribution of two daughter blastomeres from the first division of the zygote across the whole human body.

Antiobesity and Hepatoprotective Effects of Protein Hydrolysates Derived from Protaetia brevitarsis in an Obese Mouse Model.

Background: Obesity induced by excessive nutrients can cause fatty liver and metabolic dysfunction, which leads to hepatic dysfunction and local/systemic inflammatory responses. Previously, we analyzed the antioxidant, antilipotoxicity, and anti-inflammatory effects of protein hydrolysates in vitro. The aim of the present study is to investigate the antiobesity and hepatoprotective effects of protein hydrolysates derived from Protaectia brevitas (PHPB) in an obese mouse model. Methods: For this in vivo study, 40 mice were included and divided into four groups: (1) normal diet group, (2) high-fat-diet (ctrl(-)) group, (3) high-fat-diet and silymarin-treated (ctrl(+)) group, and (4) high-fat-diet and PHPB-treated group. After 6 weeks of treatment, body weight and the amount of daily food intake were observed. Moreover, the major organs and blood of animals were collected for the analysis of serum chemistry, histopathological examination, and obesity- and inflammation-related gene expressions. Results: The body weight and the amount of daily food intake significantly decreased in the PHPB-treated group compared with those in the ctrl(-) group. The levels of serum ALT, AST, ALP, creatinine, blood urea nitrogen, glucose, bilirubin, total cholesterol, TG, low-density lipoprotein, IL-6, TNF-α, and IGF-1 significantly reduced in the PHPB-treated group, whereas the serum free fatty acid, albumin, high-density lipoprotein, and adiponectin concentrations increased. In the analysis of weight of the liver, kidney, lungs, spleen, and fat tissues (from epididymal, perirenal, and mesentery tissues), the PHPB-treated group showed decreased values compared with the ctrl(-) group. In the histopathological analysis, the PHPB-treated group showed significantly reduced macrovesicular fatty change and inflammatory cell infiltration in the liver, and the size of the adipocyte in the epididymis also significantly decreased. The obesity- and inflammation-related gene (IL-6, TNF-α, IGF-1, leptin, AP2/FABP4, AMPK-α2, ß3AR, and PPAR-γ) expressions in the liver and epididymal adipose tissue were reduced in the PHPB-treated group. Conclusions: Overall, the results of this study suggest that the protein hydrolysates that derived from Protaectia brevitas produce antiobesity and hepatoprotective effects via anti-inflammatory activities.

Optimized Collagen Extraction Process to Obtain High Purity and Large Quantity of Collagen from Human Perirenal Adipose Tissue.

There is growing interest in human adipose tissue-derived collagen as a replacement for animal origin or synthetic materials. Large amounts of adipose tissues around the kidney are being discarded after kidney surgery; thus, we planned to use this tissue as a potentially ideal source of human collagen. Optimization of the collagen extraction process can contribute to the quality, quantity, supply, and cost of collagen production. To extract highly purified and concentrated collagen from human perirenal adipose tissue, we developed a novel extraction process that is superior to the conventional methods in terms of extraction yield, in vitro cytocompatibility, and physicochemical aspects. The sequence of the process and optimized conditions are as follows: (1) destaining with 0.5% H2O2 for 1 h at 4°C, (2) noncollagenous proteins elimination with 1.5 M NaOH for 24 h at 4°C, (3) atelocollagen preparation with 1.0% pepsin for 48 h at 25°C, and (4) collagen hydrolysis with 1.0 M NaOH for 10 min at 60°C. The final product showed significantly increased hydroxyproline (355.26 ± 18.71 pg/mL) and glycine (22.752 µg/mL) content than the conventional acetic acid hydrolyzed collagen (164.13 ± 1.11 pg/mL and 0.947 µg/mL, respectively). The lyophilized collagen showed more specific peaks for amides A, B, I, II, and III on FT-IR analysis and showed a further native architecture of collagen fibrils in scanning electron microscope images. Therefore, the optimized process can be an effective protocol for extracting collagen from human perirenal adipose tissue.

Multiplex Immunofluorescence Assay of Infiltrating Mononu-Clear Cell Subsets in Acute T-Cell-Mediated Rejection and BK Virus-Associated Nephropathy in the Allograft Kidney.

Renal allograft biopsy is the gold standard procedure for diagnosis of kidney rejection via specific pathological changes. To provide a better assessment of immunologic events in acute T-cell-mediated rejection (acute TCMR) and BK virus-associated nephropathy (BKVAN) cases, we used multiplex immunofluorescence staining to identify infiltrating mononuclear cell subsets in the cortex area of transplanted kidneys. Antibodies to CD4, CD8, CD20, CD68, Foxp3, and cytokeratin were used. In cortical interstitium, CD8+ cells were significantly more prevalent in acute TCMR than BKVAN cases (34% vs. 22.8%, p = 0.034). In medulla, CD20+ cells were significantly more prevalent in BKVAN than acute TCMR cases (51.9% vs. 11.3%, p = 0.028).

New-Onset Kidney Diseases after COVID-19 Vaccination: A Case Series.

Various vaccines against COVID-19 have been developed and proven to be effective, but their side effects, especially on kidney function, are not yet known in detail. In this study, we report the clinical courses and histopathologic findings of new-onset kidney diseases after COVID-19 vaccination as confirmed via kidney biopsy. Five patients aged 42 to 77 years were included in this study, and baseline kidney function was normal in all patients. The biopsy-proven diagnosis indicated newly developed kidney diseases: (1) IgA nephropathy presenting with painless gross hematuria, (2) minimal change disease presenting with nephrotic syndrome, (3) thrombotic microangiopathy, and (4) two cases of acute tubulointerstitial nephritis presenting with acute kidney injury. Individualized treatment was applied as per disease severity and underlying pathology, and the treatment outcomes of all patients were improved. Since this is not a controlled study, the specific pathophysiologic link and causality between the incidence of kidney diseases and COVID-19 vaccination are difficult to confirm. However, clinicians need to consider the possibility that kidney diseases may be provoked by vaccines in patients who have renal symptoms.

Interstitial Inflammation in the ISN/RPS 2018 Classification of Lupus Nephritis Predicts Renal Outcomes and is Associated With Bcl-2 Expression.

Objective: To investigate the histopathological characteristics of patients with lupus nephritis in the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification and assess the prognostic factors. Methods: This study enrolled 92 patients with lupus nephritis, who had conventional treatment and renal biopsy. Each renal tissue was evaluated according to 2018 ISN/RPS classification, and quantified apoptotic regulator protein, the B-cell lymphoma-2 protein (Bcl-2), expressions in selected lymphocyte subsets were measured using novel computational approaches using multicolor confocal images. Histopathological characteristics and prognostic factors of end-stage renal disease (ESRD) and chronic kidney disease (CKD) were compared. Follow-up data were obtained, and survival analysis was conducted. Results: During follow-up period (average 74.3 months), 16 and 18 patients progressed ESRD and CKD, respectively. Multivariable analysis of age, sex, disease activity and pathological features in ISN/RPS demonstrated the extent of interstitial inflammation (grade 0~3) was significantly associated with both ESRD and CKD. When interstitial inflammation was divided into mild (grade 0, 1) and severe (grade 2, 3), Cox regression analysis showed that patients with severe interstitial inflammation were significantly increased risk of both ESRD and CKD (hazard ratio 4.67 and 3.8, respectively). Bcl-2 expression in CD4+ and CD20 cells was significantly higher in the severe interstitial inflammation group compared to in mild interstitial inflammation patients (p=0.006 and 0.010, respectively). Conclusion: The extent of interstitial inflammation can predict clinical renal outcomes. Significantly elevated Bcl-2 expression in both CD4+ and CD20 cells was found in severe interstitial inflammation compared with mild interstitial inflammation.

Activation of Complement System in Henoch-Schönlein Purpura Nephritis.

Introduction: We studied the association between Henoch-Schönlein purpura nephritis (HSPN) and complement system activation. Methods: We retrospectively reviewed the pathologic findings and medical records of 35 children and 12 adults with HSPN and compared the differences according to C4d positivity in three groups consisting of total 47 patients, 35 pediatric and 12 adult patients, respectively. C4d staining of renal biopsy was additionally performed at the time of diagnosis or retrospectively using archival biopsy material. Results: The overall rate of C4d positivity was 53.2%: 20 (57.1%) of the 35 children and five (41.7%) of the 12 adults. Among the groups there was no significant difference in the severity of proteinuria, renal function, presence of crescents or mesangial proliferation stratified by C4d positivity, unlike IgA nephropathy. Conclusions: We suggest that the activation of complement system is not correlated with the clinical or pathological severity of HSPN.

Influence of Irradiation on Capsules of Silicone Implants Covered with Acellular Dermal Matrix in Mice.

BACKGROUND: In advanced breast cancer, radiotherapy is recommended as adjuvant therapy following breast reconstructive surgery. This inevitably led to growing concerns over possible complications of radiotherapy on implants. In this experimental animal study, we investigated the utility of acellular dermal matrix (ADM) wraps around implants as preventive management for radiotherapy complications. METHODS: Black mice (C57NL6; n = 32) were assigned to groups that either received radiation or did not: groups A and B underwent surgery using implants without radiotherapy; while groups C and D underwent surgery using implants with radiotherapy for one and three months, respectively. The hemispheric silicone implants with an 0.8-cm-diameter were inserted on the left back of each mouse, and implants wrapped by ADM were inserted on the right back. The Clinic 23EX LINAC model was used for irradiation at 10 Gy. The samples were evaluated by gross assessment, histological analysis, immunohistochemical analysis, and the Western blotting test. RESULTS: The H&E staining analysis showed that membrane thickness is smallest in group A, followed by groups C, D, and B. In a Masson trichrome histological analysis, collagen fibers became less dense and more widespread over time in the groups that received an ADM. Immunohistochemistry findings were similarly constant. However, the expression of TGF-ß1 was increased in the irradiated groups, whereas it was decreased in the non-irradiated groups as observed over time. CONCLUSIONS: Radiotherapy was shown to increase risk factors for capsular contracture, including inflammatory response, pseudoepithelium, thinning of membrane, and TGF-ß1 expression over time; however, the accompanying framework using an ADM as a barrier between implant and tissue was shown to be effective in alleviating these risks. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .